Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1

One of the major signaling pathways by which extracellular signals induce cell proliferation and differentiation involves the activation of extracellular signal-regulated kinases (ERKs). Because calmodulin is essential for quiescent cells to enter cell cycle, the role of calmodulin on ERK2 activatio...

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Autores: Bosch i Rodríguez, Marta, Gil i Santano, Joan, Bachs Valldeneu, Oriol, Agell i Jané, Neus
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1998
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177102
Acceso en línea:https://hdl.handle.net/2445/177102
Access Level:acceso abierto
Palabra clave:Calmodulina
Metabolisme
Ciclines
Sulfamides
Calmodulin
Metabolism
Cyclins
Sulfonamides
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spelling Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1Bosch i Rodríguez, MartaGil i Santano, JoanBachs Valldeneu, OriolAgell i Jané, NeusCalmodulinaMetabolismeCiclinesSulfamidesCalmodulinMetabolismCyclinsSulfonamidesOne of the major signaling pathways by which extracellular signals induce cell proliferation and differentiation involves the activation of extracellular signal-regulated kinases (ERKs). Because calmodulin is essential for quiescent cells to enter cell cycle, the role of calmodulin on ERK2 activation was studied in cultured fibroblasts. Serum, phorbol esters, or active Ras induced ERK2 activation in NIH 3T3 fibroblasts. This activation was not inhibited by calmodulin blockade. Surprisingly, inhibition of calmodulin prior to fetal bovine serum addition prolonged activation of ERK2. Furthermore, inactivation of calmodulin in serum-starved cells induced ERK2 phosphorylation that was dependent on MAP kinase kinase (MEK). Inactivation of calmodulin in serum-starved cells also induced activation of Ras, Raf, and MEK. On the contrary, tyrosine phosphorylation of tyrosine kinase receptors was not observed. These results indicate that calmodulin inhibits ERK2 activation pathway at the level of Ras. Calmodulin inhibition induced overexpression of p21(cip1) which was dependent on MEK activity. We propose that inhibition of Ras by calmodulin prevents the activation of ERK2 at low serum concentration. Thus, entering into the cell cycle after serum addition would imply the overcoming of the inhibitory effect of calmodulin and consequently ERK2 activation. Furthermore, down-regulation of Ras by calmodulin may be also important to determine the duration of ERK2 activation and to prevent a high p21(cip1) expression that would lead to an inhibition of cell proliferation.American Society for Biochemistry and Molecular Biology2021202119982021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion6 p.application/pdfhttps://hdl.handle.net/2445/177102Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1074/jbc.273.34.22145Journal of Biological Chemistry, 1998, vol. 273, num. 34, p. 22145-22150https://doi.org/10.1074/jbc.273.34.22145(c) American Society for Biochemistry and Molecular Biology, 1998info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1771022026-05-29T05:05:01Z
dc.title.none.fl_str_mv Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
title Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
spellingShingle Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
Bosch i Rodríguez, Marta
Calmodulina
Metabolisme
Ciclines
Sulfamides
Calmodulin
Metabolism
Cyclins
Sulfonamides
title_short Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
title_full Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
title_fullStr Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
title_full_unstemmed Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
title_sort Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21CIP1
dc.creator.none.fl_str_mv Bosch i Rodríguez, Marta
Gil i Santano, Joan
Bachs Valldeneu, Oriol
Agell i Jané, Neus
author Bosch i Rodríguez, Marta
author_facet Bosch i Rodríguez, Marta
Gil i Santano, Joan
Bachs Valldeneu, Oriol
Agell i Jané, Neus
author_role author
author2 Gil i Santano, Joan
Bachs Valldeneu, Oriol
Agell i Jané, Neus
author2_role author
author
author
dc.subject.none.fl_str_mv Calmodulina
Metabolisme
Ciclines
Sulfamides
Calmodulin
Metabolism
Cyclins
Sulfonamides
topic Calmodulina
Metabolisme
Ciclines
Sulfamides
Calmodulin
Metabolism
Cyclins
Sulfonamides
description One of the major signaling pathways by which extracellular signals induce cell proliferation and differentiation involves the activation of extracellular signal-regulated kinases (ERKs). Because calmodulin is essential for quiescent cells to enter cell cycle, the role of calmodulin on ERK2 activation was studied in cultured fibroblasts. Serum, phorbol esters, or active Ras induced ERK2 activation in NIH 3T3 fibroblasts. This activation was not inhibited by calmodulin blockade. Surprisingly, inhibition of calmodulin prior to fetal bovine serum addition prolonged activation of ERK2. Furthermore, inactivation of calmodulin in serum-starved cells induced ERK2 phosphorylation that was dependent on MAP kinase kinase (MEK). Inactivation of calmodulin in serum-starved cells also induced activation of Ras, Raf, and MEK. On the contrary, tyrosine phosphorylation of tyrosine kinase receptors was not observed. These results indicate that calmodulin inhibits ERK2 activation pathway at the level of Ras. Calmodulin inhibition induced overexpression of p21(cip1) which was dependent on MEK activity. We propose that inhibition of Ras by calmodulin prevents the activation of ERK2 at low serum concentration. Thus, entering into the cell cycle after serum addition would imply the overcoming of the inhibitory effect of calmodulin and consequently ERK2 activation. Furthermore, down-regulation of Ras by calmodulin may be also important to determine the duration of ERK2 activation and to prevent a high p21(cip1) expression that would lead to an inhibition of cell proliferation.
publishDate 1998
dc.date.none.fl_str_mv 1998
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177102
url https://hdl.handle.net/2445/177102
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.273.34.22145
Journal of Biological Chemistry, 1998, vol. 273, num. 34, p. 22145-22150
https://doi.org/10.1074/jbc.273.34.22145
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 1998
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 1998
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 6 p.
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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